Title:Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin-
Resistant Gastric Cancer SGC7901/DDP Cells
Volume: 22
Issue: 2
Author(s): Dongmei Zhan, Tengyang Ni, Haibo Wang, Mengying Lv, Masataka Sunagawa and Yanqing Liu*
Affiliation:
- Institute of Translational Medicine, Medical College, Yangzhou University, The Key Laboratory of Syndrome Differentiation and
Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, 225001, PR China
Keywords:
Gastric cancer, drug resistance, celastrol, mTOR signaling pathway, cisplatin, SGC7901.
Abstract: Background: This study aimed to determine the effect and mechanism of Celastrol inhibiting the
proliferation and decreasing the drug resistance of cisplatin-resistant gastric cancer cells.
Objective: The objective of this study was to explore the effect and mechanism of Celastrol on proliferation and
drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP.
Methods: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatinresistant
cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug Resistance Index (DRI). According
to the half Inhibitory Concentration (IC50) value, the action of the concentration of the following experimental
drugs was set to reduce the cytotoxicity. Annexin V-FITC/PI double staining method was used to detect the
apoptosis of SGC7901/DDP cells induced by Celastrol. Western Blot was used to examine the expression levels
of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated
Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin
(mTOR) pathway-related proteins. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR)
was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP.
Results: (1) Compared with the control group (we set the untreated group as the control group), the proliferation
of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4μmol/L Celastrol in a time- and
concentration-dependent manner (P<0.05). The Drug Resistance Index (DRI) of the SGC7901/DPP cells to
DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and
induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp,
MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However,
after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells
were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced
the expression of the mTOR signaling pathway-related proteins, suggesting that the mTOR signaling pathway
may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing
their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp,
MRP1, and BCRP in the SGC7901/DPP cells.
Conclusion: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce
the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the
mTOR signaling pathway.
